Copper‐Catalyzed Electrophilic Thiolation of Organozinc Halides by Using N‐Thiophthalimides Leading to Polyfunctional Thioethers

• Published in: Chemistry : a European journal Vol. 25; no. 15; pp. 3752 - 3755
• Main Authors: Graßl, Simon, Hamze, Clémence, Koller, Thaddäus J., Knochel, Paul
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 12.03.2019; Wiley Subscription Services, Inc
• Subjects: Aromatic compounds; Cathepsin D; Chemistry; Chemistry, Multidisciplinary; Copper; copper catalysis; electrophilic thiolation; Halides; organozinc halides; Physical Sciences; Science & Technology; Thiocyanates; Thioethers; trifluoromethylthioation; Zinc; PALLADIUM; DIARYL; VINYL SULFIDES; ALKYNES; ORGANOMETALLICS; electrophilic thiolation; DISULFIDES; BORONIC ACIDS; copper catalysis; TRIFLUOROMETHYLTHIOLATION; organozinc halides; thioethers; ARYL HALIDES; trifluoromethylthioation; GRIGNARD-REAGENTS
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201806261

(Hetero)aryl, benzylic, and alkyl zinc halides were thiolated with N‐thiophthalimides at 25 °C within 1 h in the presence of 5–10 % Cu(OAc)2⋅H2O to furnish the corresponding polyfunctionalized thioethers in good yields. This electrophilic thiolation was extended to the introduction of trifluoromethylthio (SCF3), thiocyanate (SCN), and selenophenyl (SePh) groups. The utility of this method was shown in a seven‐step synthesis of a potent cathepsin D inhibitor in 34 % overall yield. (Hetero)aryl, benzylic, and alkyl zinc halides were thiolated with N‐thiophthalimides at 25 °C in the presence of 5–10 % Cu(OAc)2⋅H2O to give polyfunctionalized thioethers in 55–98 % yields (see scheme). This electrophilic thiolation was extended to the introduction of trifluoromethylthio (SCF3), thiocyanate (SCN), and selenophenyl (SePh) groups. The utility of this method was shown in the seven‐step synthesis of a potent cathepsin D inhibitor in 34 % overall yield.